Original ArticleComparison of Candesartan and Angiotensin-(1-7) Combination to Mito-TEMPO Treatment for Normalizing Blood Pressure and Sympathovagal Balance in (mREN2)27 RatsNautiyal, Manisha PhD*; Shaltout, Hossam A. PhD*,†; Chappell, Mark C. PhD*,‡; Diz, Debra I. PhD*,‡Author Information *Hypertension & Vascular Research, Cardiovascular Sciences Center, Wake Forest University School of Medicine, Winston-Salem, NC; and Departments of †Obstetrics and Gynecology; and ‡General Surgery, Wake Forest University School of Medicine, Winston-Salem, NC. Reprints: Debra I. Diz, PhD, The Hypertension & Vascular Research, Wake Forest School of Medicine, Biotech Place, 575 Patterson Ave, Winston-Salem, NC 27101 (e-mail: [email protected]). Funding from COSEHC Warren Trust (M.N.), American Heart Association Postdoctoral Fellowship (M.N.), Farley Hudson Foundation of Jacksonville, NC, Hypertension and Vascular Research Funds, and National Institutes of Health (D.I.D. and M.C.C.: HL-51952 and HL-56973) provided support for this project. The authors report no conflicts of interest. Journal of Cardiovascular Pharmacology: March 2019 - Volume 73 - Issue 3 - p 143-148 doi: 10.1097/FJC.0000000000000645 Buy Metrics Abstract Hypertensive transgenic (mRen2)27 rats exhibit impaired baroreflex sensitivity (BRS) for control of heart rate (HR). Intracerebroventricular infusion of Ang-(1-7) improves indices of vagal BRS independent of lowering mean arterial pressure (MAP), whereas AT1 receptor blockade normalizes MAP and indices of sympathetic tone without correcting the vagal BRS. Scavenging cellular reactive oxygen species (ROS) with tempol in brain fails to correct either hypertension or sympathovagal balance in these animals, despite reports that mitochondrial ROS contributes to Ang II–infusion hypertension. To examine effects of a putative preferential mitochondrial ROS scavenger in the brain of (mRen2)27 rats, ICV infusions of Mito-TEMPO (3.2 μg/2.5 μL/h) were compared with artificial cerebrospinal fluid (aCSF; 2.5 μL/h) and combination AT1 receptor antagonist candesartan (CAN: 4 μg/2.5 μL/h) plus Ang-(1-7) (0.1 μg/2.5 μL/h) treatment. MAP was lower after CAN + Ang-(1-7) treatment, and both vagal and sympathetic components of BRS and sympathovagal balance were improved. By contrast, Mito-TEMPO improved sympathetic components of BRS and tended to improve overall sympathovagal balance but failed to alter MAP in this model of hypertension. Although further studies are required to determine whether Mito-TEMPO or CAN + Ang-(1-7) treatment at the doses used altered mitochondrial ROS, optimal therapeutic benefits are achieved by shifting the balance from Ang II toward Ang-(1-7) in this model of chronic RAS-dependent hypertension. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.